Project Summary Several factors contribute to nicotine dependence, but dysregulation of brain circuits underlying reward sen- sitivity play a fundamental role. Chronic drug use is thought to result in the attribution of excessive motiva- tional value to drugs at the expense of natural rewards. The neurobiological processes mediating reduced sensitivity to natural rewards are still obscure. We don't know whether brain reward sensitivity differences are already present in young smokers or whether these differences develop only after long-term nicotine use. Furthermore, we do not yet know how brain reward sensitivity differences are related to behavioral and sub- jective measures of hedonic capacity (i.e., the tendency to not enjoy pleasurable activities). The objective of this proposal is to assess the feasibility of using a newly discovered neural biomarker to characterize youths' individual differences in reward sensitivity. Our central hypothesis is that young smokers will already show blunted brain responses to natural rewards and that these differences will correlate with behavioral and self- report measures of hedonic capacity. To test this hypothesis we will assess reward sensitivity in young smokers and never smokers using dense array event-related potentials (ERPs), behavioral, and self-report measures. This multi-modal approach will allow us to link subjective and behavioral variation in hedonic ca- pacity to its neural underpinnings. We will achieve our objective by pursuing the following Specific Aims: 1) Characterize in young smokers the behavioral correlates of brain reward sensitivity; 2) Determine the role exerted by nicotine on youths' reward sensitivity. Our approach is innovative because the multimodal as- sessment proposed here will allow us to investigate the relationships existing among neurobiological, behav- ioral, and subjective domains of the reward-processing construct and to determine how nicotine alters them in young smokers. Determining in youths how neural, behavioral, and subjective measures of reward sensi- tivity interrelate is significant because it is the necessary preliminary step to understanding how individual dif- ferences in hedonic capacity confer vulnerability to nicotine dependence. The results of this project will con- tribute to the development of new and effective evidence-based prevention strategies for individuals at risk, and to the creation of more successful interventions to promote abstinence in individuals already addicted.